Adjuvant Therapy with Durvalumab Shows Promise in Advanced Esophageal Cancer
San Francisco, CA—Adjuvant treatment with durvalumab (Imfinzi), a checkpoint inhibitor, in patients with residual disease after trimodal therapy for advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma was associated with a 79% 1-year relapse-free survival rate in a phase 2 clinical trial. Historically, the 1-year relapse rate has been 50% in patients with GEJ carcinoma who do not achieve a pathologic complete response with trimodal therapy, even with additional chemotherapy, said Hirva Mamdani, MD, Thoracic Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI, at the 2019 Gastrointestinal Cancers Symposium.
Chemoradiation followed by esophagectomy is the standard of care for patients with locally advanced esophageal or GEJ adenocarcinoma, but typically only 30% of patients achieve a pathologic complete response with this approach.
“Patients who do not achieve a pathologic complete response and those who have persistent disease in the lymph nodes are at a higher risk of relapse,” said Dr Mamdani. “So far, no adjuvant therapies have been shown to improve survival in this patient population. We are in real need for novel treatment strategies.”
Immune checkpoint inhibitors have demonstrated activity in metastatic PD-L1–positive esophageal adenocarcinoma, she said. Preclinical studies have shown upregulation of the PD-1 pathway with radiation, with or without chemotherapy, forming the rationale for this present study.
Dr Mamdani presented data from the single-arm, multicenter, investigator-initiated Big Ten Cancer Research Consortium study of 24 patients (10 with distal esophageal adenocarcinoma and 14 with GEJ adenocarcinoma) who had residual disease after neoadjuvant chemoradiation and microscopically margin-negative resection.
Of the 24 patients, 19 (79%) had lymph node involvement at the time of surgery; the other 5 patients had node-negative disease. The patients’ median age was 60 years, and all but 1 patient were men. Of the 24 patients, 18 had received previous treatment with carboplatin plus paclitaxel concurrently with radiation and 6 had received cisplatin plus 5-fluorouracil.
After esophagectomy, all patients received durvalumab 1500 mg intravenously every 4 weeks for up to 1 year (ie, 13 doses). Patients who completed treatment and those who discontinued treatment for reasons other than disease relapse were followed for 1 year.
Overall, 12 patients completed 1 year of durvalumab therapy and 12 patients discontinued treatment before 1 year; 6 patients discontinued treatment because of disease relapse, 5 because of adverse events, and 1 withdrew consent. The median number of treatment cycles was 12.5.
“The efficacy results are very encouraging in this high-risk patient population,” said Dr Mamdani. After a median follow-up of 14.5 months, the 1-year relapse-free survival rate was 79.2%.
Good Safety Profile
The safety profile of durvalumab was consistent with previous reports; 3 (12.5%) patients had grade 3 treatment-related adverse events (pneumonitis, colitis, and hepatitis) leading to treatment discontinuation. No grade 4 side effects were reported.
The most common (≥10%) grade 1 and 2 adverse events were fatigue (33.3%), nausea (25.0%), cough (20.8%), diarrhea (16.7%), and pruritus (16.7%).
“Adjuvant durvalumab in patients with persistent residual disease in the surgical sample following trimodality therapy for locally advanced esophageal adenocarcinoma was feasible,” Dr Mamdani concluded. This study, she noted, will be expanded to enroll an additional 14 patients.